C-reactive protein (CRP), a marker of systemic inflammation, has been reported to be an independent predictor of cardiovascular disease in both women and men. We recently published data from cross-sectional analyses showing that CRP is inversely related to cardiorespiratory fitness, and that this association is independent of body mass index. The possibility that regular exercise may affect CRP presents an intervention to evaluate for reducing elevated CRP. Though there are a number of studies focusing on related topics, to our knowledge there are no published reports from randomized clinical trials on the effect of exercise training alone on CRP. The goal of the proposed study, Inflammation and Exercise (INFLAME), is to determine the effect of exercise training on elevated (equal to or greer than 2.0 mg/L) CRP concentrations in initially sedentary women and men (18 to 75 years old). We will randomly assign 170 individuals equally to a no exercise control group or to an exercise group. Exercising individuals will participate in 3 or 4 training sessions each week for 4 months progressing to a total energy expenditure of 16 kcal . kg(-1) . week(-1), which is an exercise dose at the upper end of current public health recommendations for physical activity. The target exercise intensity will be 50-70% of baseline VO2 max. The primary outcome measure is plasma CRP concentration. Secondary outcomes are changes in variables that are potential mechanisms whereby regular exercise might reduce CRP. These include visceral adiposity, the cytokines IL-6 and TNF-alpha, and heart rate variability as a measure of autonomic balance. An additional strength of this proposed study is that although the primary outcome is CRP, this study would also contribute significantly to the limited body of literature examining the effect of exercise on the variables of visceral adiposity, cytokines, and heart rate variability.